title: Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation.
abstract: Omega-3 fatty acids (ω-3 FAs) have potential anti-inflammatory activity in a variety of inflammatory human diseases, but the mechanisms remain poorly understood. Here we show that stimulation of macrophages with ω-3 FAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and other family members, abolished NLRP3 inflammasome activation and inhibited subsequent caspase-1 activation and IL-1β secretion. In addition, G protein-coupled receptor 120 (GPR120) and GPR40 and their downstream scaffold protein β-arrestin-2 were shown to be involved in inflammasome inhibition induced by ω-3 FAs. Importantly, ω-3 FAs also prevented NLRP3 inflammasome-dependent inflammation and metabolic disorder in a high-fat-diet-induced type 2 diabetes model. Our results reveal a mechanism through which ω-3 FAs repress inflammation and prevent inflammation-driven diseases and suggest the potential clinical use of ω-3 FAs in gout, autoinflammatory syndromes, or other NLRP3 inflammasome-driven inflammatory diseases.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Anhui 230027, China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Yan
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Thibaud
authors.initials: T
authors.lastname: Spinetti
authors.forename: Aubry
authors.initials: A
authors.lastname: Tardivel
authors.forename: Rosa
authors.initials: R
authors.lastname: Castillo
authors.forename: Carole
authors.initials: C
authors.lastname: Bourquin
authors.forename: Greta
authors.initials: G
authors.lastname: Guarda
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.forename: Jurg
authors.initials: J
authors.lastname: Tschopp
authors.forename: Rongbin
authors.initials: R
authors.lastname: Zhou
mesh_terms: D000818:Animals; D019390:Arrestins / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D059305:Diet, High-Fat / Q000009:adverse effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D015525:Fatty Acids, Omega-3 / Q000276:immunology; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism*; D007249:Inflammation / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
chemical_list: C000605254:ARRB2 protein, human; C000605258:Arrb2 protein, mouse; D019390:Arrestins; D002352:Carrier Proteins; C498007:FFAR4 protein, mouse; D015525:Fatty Acids, Omega-3; C473036:Ffar1 protein, mouse; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D043562:Receptors, G-Protein-Coupled; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D020170:Caspase 1